In controlled drug delivery systems, well-characterized and reproducible dosage forms are utilized to ensure that the rate and duration of drug delivery achieves the required concentration in the host. Usually there is a concentration range for each drug which provides optimal therapeutic effects: higher concentration may cause toxicity whereas a lower one may be therapeutically ineffective. Controlled delivery is usually achieved by a number of methods; two common ones employ either a matrix system where the drug is dispersed in a polymer matrix or a microencapsulation system where the individual drug particle is encapsulated in a polymeric coating. The polymeric coating can also provide protection for fragile drugs from hydrolysis and degradation for example by providing protection from stomach acids.
The size range of drug particles can vary between micron-sized, sub-micron and nanoparticles. Due to their greater solubility, high stability, high carrier capacity, incorporation of biodegradable and hydrophobic/hydrophilic substances and administration by a variety of delivery vehicles, nanoparticle-based systems have attracted considerable attention in controlled release of drugs, delivery of anticancer drugs and imaging agents to tumors, tuberculosis treatment and as non-viral gene delivery vehicles. When coated with lower molecular weight polyethylene glycol, nanoparticles could traverse the physiological human mucous rapidly. Dense polyethylene glycol coating improved penetration of polymeric nanoparticles within brain tissue in cases where the blood-brain barrier is compromised. Polymer-coated nanoparticles are also being utilized in chemical, electronic, optical and physical applications.
A variety of methods have been conventionally employed to coat micron-sized, submicron and nanoparticles with a polymer. Physical vapor deposition, plasma treatment, chemical vapor deposition, and pyrolysis of polymeric organic materials are examples of dry methods, and sol-gel processes, emulsification and solvent evaporation techniques are examples of wet methods. Additional methods for polymer coating or encapsulation of nanoparticles and ultrafine particles employing supercritical CO2 include: Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti-Solvent (SAS), and Gas Anti-Solvent (GAS) processes. These processes have many shortcomings, such as very high pressures, and low solubility of polymers (many of which may also lack biodegradability). Furthermore, these are batch processes and it is problematic to develop the needed drug production capacities.
Although fluidized bed-based coating processes can be continuous, there are problems due to scale-up difficulties as well as agglomeration of smaller (submicron and nano) particles resulting from van der Waals and other inter-particle forces; the polymer coating will enhance the agglomeration tendencies. Conventional batch crystallization devices, if used for coating, will suffer from imperfect mixing and non-uniform conditions leading to extreme variability of the product.
Conventional crystallization/precipitation typically relies on processes employing cooling, solvent evaporation, anti-solvent addition and precipitation by reaction. For anti-solvent addition-based processes, a technique of increasing interest in pharmaceutical processing is the use of an impinging-jet mixer, where two high velocity streams are brought into contact to effect high nucleation rates, followed by growth in a well-mixed vessel or a tubular precipitator. There are a number of well-known shortcomings of this technique. As referenced above, the SAS, GAS and related supercritical anti-solvent techniques are batch processes which require very demanding experimental conditions.
Despite efforts to date, a need remains for efficient and effective systems and methods to continuously coat submicron and nano-sized particles. In particular, a need remains for systems and methods for effective coating of submicron and nano-sized drug particles. These and other needs are addressed according to the present disclosure.